The shared allelic architecture of adiponectin levels and coronary artery disease

Objective: A large body of epidemiologic data strongly suggests an association between excess adiposity and coronary artery disease (CAD). Low adiponectin levels, a hormone secreted only from adipocytes, have been associated with an increased risk of CAD in observational studies. However, these associations cannot clarify whether this relationship is causal or due to a shared set of causal factors or even confounding. Genome-wide association studies have identified common variants that influence adiponectin levels, providing valuable tools to examine the genetic relationship between adiponectin and CAD. Methods: Using 145 genome wide significant SNPs for adiponectin from the ADIPOGen consortium (. n=49,891), we tested whether adiponectin-decreasing alleles influenced risk of CAD in the CARDIoGRAM consortium (. n=85,274). Results: In single-SNP analysis, 5 variants among 145 SNPs were associated with increased risk of CAD after correcting for multiple testing (P<4.4×10^-4). Using a multi-SNP genotypic risk score to test whether adiponectin levels and CAD have a shared genetic etiology, we found that adiponectin-decreasing alleles increased risk of CAD (P=5.4×10^-7). Conclusion: These findings demonstrate that adiponectin levels and CAD have a shared allelic architecture and provide rationale to undertake a Mendelian randomization studies to understand if this relationship is causal.